P944: REAL-WORLD PATIENT CHARACTERISTICS AND SURVIVAL OUTCOMES OF LENALIDOMIDE REFRACTORY VS. LENALIDOMIDE EXPOSED RRMM PATIENTS IN THE HONEUR FEDERATED DATA NETWORK
Authors: Ivan Spicka, Ido Lapidot, Maximilian Merz, Jakub Radocha, Martin Stork, Tomas Jelínek, Alexandra Jungova, Jiri Minarik, Jan Soukup, Michel Van Speybroeck, Nolen Perualila, Joris Diels, João Duarte Mendes, Kirsten van Nimwegen, Kai Strobel, Sebastien Wischlen, Henrik Sliwka, Blanca Gros Otero, Roman Hajek
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Treatment options that became available over the past two decades, including proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and monoclonal antibodies have significantly improved survival outcomes of patients with multiple myeloma (MM). However, MM is still mostly an incurable disease and patients ultimately progress and become refractory to standard treatments. The increased use of lenalidomide (Len) containing regimens in the frontline treatment setting has led to a higher number of Len-refractory patients in the 2nd-4th lines of therapy (LOT) setting. (Moreau P, Blood Cancer J 2019). However, still limited data is available on baseline characteristics and survival outcomes of real-world European MM patients who have been exposed to Len and become refractory or not. Aims: Describe baseline characteristics and overall-survival (OS) difference between Len-refractory and Len-exposed non-refractory MM patients in 2nd-4th LOT in the real-world setting. Methods: Data from the Registry of Monoclonal Gammopathies (Czech Republic) and the Oncology Information Service registry (Germany) was analyzed in HONEUR, which is a federated data network with patient level data solely stored and governed at local sites with analysis executed centrally, which gives a unique advantage of increasing the sample size for infrequent patient subgroups. The applied method involved an upfront harmonization of the two distinct datasets to a common data model; OMOP CDM v5.3. A centrally developed script was executed to both local data-sources from which aggregate level results were then combined centrally. MM patients exposed to both a PI and Len, in 2nd-4th lines of therapy and with ECOG 0-1, treated between 2015 and 2021 were identified to compare outcomes of Len-exposed, non-refractory versus Len-refractory patients. Refractoriness to Len was defined as disease progression while on Len and/or initiation of subsequent LOT not containing Len within 60 days after stopping the previous Len-containing LOT. Patients fulfilling the eligibility criteria at multiple times in their longitudinal follow-up were included as separate observations with LOT as unit of analysis. Results: A total of 2415 treatment lines were included in the analysis. Of these, 2029 (84.0 %) were from Len-refractory patients. Median follow-up from index date was 22.0 vs 23.5 months for the Len-exposed non-refractory and Len-refractory patients, respectively. Baseline characteristics were generally comparable between the Len-exposed non-refractory and Len-refractory cohorts and will be fully described in the final poster. Median OS for Len -refractory and Len-exposed non-refractory patients was 21.5 [95% CI:19.94; 23.06] vs. 36.6 [95% CI: 31.74; 43.53] months, respectively, with a Hazard Ratio (HR) of 1.89 [95% CI: 1.57; 2.27], p<0.001. (Figure 1a). After adjusting for treatment line, OS was still significantly worse in the Len refractory patients, with risk of death 71% higher compared to the Len-exposed non refractory patients (HR: 1.71 [1.42, 2.06]. The increased risk of death in the Len-refractory vs Len-exposed non-refractory patients was more pronounced in 2nd LOT (HR=1.82 [1.00, 3.27]). (Figure 1b). Summary/Conclusion: Analysis conducted on European patients in the HONEUR federated data network confirms the worse survival prognosis and higher clinical unmet need of MM patients who have become refractory to Len compared to Len-exposed non-refractory patients in the real-world setting. Effective new treatments that can prolong survival for Len-refractory patients are needed.Keywords: Real world data, Multiple myeloma